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Cocaine-mediated impact on HIV infection in humanized BLT mice.

Kim SG, Lowe EL, Dixit D, Youn CS, Kim IJ, Jung JB, Rovner R, Zack JA, Vatakis DN - Sci Rep (2015)

Bottom Line: Cocaine abuse has been shown to have broad-ranging effects on human immunity.Moreover, cohort studies in the pre- and post-HAART era have linked stimulant abuse with increased HIV pathogenesis.Stimulant exposure resulted in increased inflammatory cytokine expression, accelerated HIV infection, while blunting effector function of cytotoxic T lymphocytes.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Medicine, Division of Hematology-Oncology [2] UCLA AIDS Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095.

ABSTRACT
Cocaine abuse has been shown to have broad-ranging effects on human immunity. With regards to HIV infection, in vitro studies have shown that cocaine enhances infection of stimulated lymphocytes. Moreover, cohort studies in the pre- and post-HAART era have linked stimulant abuse with increased HIV pathogenesis. The latter data, however, have been undermined by a series of confounding factors underscoring the importance of controlled in vivo models to fully assess the impact of cocaine use and abuse on HIV infection and pathogenesis. Here, we have infected humanized mice with HIV-1 following acute cocaine exposure to assess the impact on infection. Stimulant exposure resulted in increased inflammatory cytokine expression, accelerated HIV infection, while blunting effector function of cytotoxic T lymphocytes. These data demonstrate cocaine's multifactorial impact on HIV infection that extends beyond high-risk behavior.

No MeSH data available.


Related in: MedlinePlus

Increased activation persists in the cocaine treated, HIV infected animals.Splenocytes from the sacrificed mice were also used for flow cytometric analysis of lymphocyte phenotype. The COCAINE-HIV group of mice has higher levels of (a) CD4CD38 and (b) CD8CD38. (c) To assess functionality of CD8 T cells, we stimulated ex vivo splenocytes in the presence of GolgiPlug to measure levels of IFN-γ production. The COCAINE-HIV group had comparable levels to HIV despite the higher numbers of CD8CD38 T cells. For all figures, *p < 0.05, **p < 0.01, using Mann-Whitney or Kruskal-Wallis test (for 3 or more groups).
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f4: Increased activation persists in the cocaine treated, HIV infected animals.Splenocytes from the sacrificed mice were also used for flow cytometric analysis of lymphocyte phenotype. The COCAINE-HIV group of mice has higher levels of (a) CD4CD38 and (b) CD8CD38. (c) To assess functionality of CD8 T cells, we stimulated ex vivo splenocytes in the presence of GolgiPlug to measure levels of IFN-γ production. The COCAINE-HIV group had comparable levels to HIV despite the higher numbers of CD8CD38 T cells. For all figures, *p < 0.05, **p < 0.01, using Mann-Whitney or Kruskal-Wallis test (for 3 or more groups).

Mentions: To further characterize the impact of cocaine on immunity during early acute HIV infection, we analyzed tissue samples for various immunological parameters such as T cell activation and plasma cytokine levels. Splenocytes of humanized mice with detectable viral loads were analyzed for T cell activation. Based on our data, the COCAINE-HIV group had elevated CD4+CD38+ T cells (Fig. 4a). Interestingly, the levels of activated CD8+CD38+ T cells were also higher in these animals (Fig. 4b). Since we detected increased levels of CD8+CD38+ T cells in the COCAINE-HIV group, we examined whether this increased activation would translate to robust effector cytokine release after ex vivo stimulation. This would suggest that the effector functions during early acute infection in the presence of cocaine may not be impaired. Thus, we stimulated ex vivo splenocytes from these cohorts using PMA/Ionomycin for 3 days. The COCAINE-HIV group did not exhibit significantly higher levels of IFN-γ production from the HIV only group despite the more activated phenotype (Fig. 4c).


Cocaine-mediated impact on HIV infection in humanized BLT mice.

Kim SG, Lowe EL, Dixit D, Youn CS, Kim IJ, Jung JB, Rovner R, Zack JA, Vatakis DN - Sci Rep (2015)

Increased activation persists in the cocaine treated, HIV infected animals.Splenocytes from the sacrificed mice were also used for flow cytometric analysis of lymphocyte phenotype. The COCAINE-HIV group of mice has higher levels of (a) CD4CD38 and (b) CD8CD38. (c) To assess functionality of CD8 T cells, we stimulated ex vivo splenocytes in the presence of GolgiPlug to measure levels of IFN-γ production. The COCAINE-HIV group had comparable levels to HIV despite the higher numbers of CD8CD38 T cells. For all figures, *p < 0.05, **p < 0.01, using Mann-Whitney or Kruskal-Wallis test (for 3 or more groups).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4471720&req=5

f4: Increased activation persists in the cocaine treated, HIV infected animals.Splenocytes from the sacrificed mice were also used for flow cytometric analysis of lymphocyte phenotype. The COCAINE-HIV group of mice has higher levels of (a) CD4CD38 and (b) CD8CD38. (c) To assess functionality of CD8 T cells, we stimulated ex vivo splenocytes in the presence of GolgiPlug to measure levels of IFN-γ production. The COCAINE-HIV group had comparable levels to HIV despite the higher numbers of CD8CD38 T cells. For all figures, *p < 0.05, **p < 0.01, using Mann-Whitney or Kruskal-Wallis test (for 3 or more groups).
Mentions: To further characterize the impact of cocaine on immunity during early acute HIV infection, we analyzed tissue samples for various immunological parameters such as T cell activation and plasma cytokine levels. Splenocytes of humanized mice with detectable viral loads were analyzed for T cell activation. Based on our data, the COCAINE-HIV group had elevated CD4+CD38+ T cells (Fig. 4a). Interestingly, the levels of activated CD8+CD38+ T cells were also higher in these animals (Fig. 4b). Since we detected increased levels of CD8+CD38+ T cells in the COCAINE-HIV group, we examined whether this increased activation would translate to robust effector cytokine release after ex vivo stimulation. This would suggest that the effector functions during early acute infection in the presence of cocaine may not be impaired. Thus, we stimulated ex vivo splenocytes from these cohorts using PMA/Ionomycin for 3 days. The COCAINE-HIV group did not exhibit significantly higher levels of IFN-γ production from the HIV only group despite the more activated phenotype (Fig. 4c).

Bottom Line: Cocaine abuse has been shown to have broad-ranging effects on human immunity.Moreover, cohort studies in the pre- and post-HAART era have linked stimulant abuse with increased HIV pathogenesis.Stimulant exposure resulted in increased inflammatory cytokine expression, accelerated HIV infection, while blunting effector function of cytotoxic T lymphocytes.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Medicine, Division of Hematology-Oncology [2] UCLA AIDS Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095.

ABSTRACT
Cocaine abuse has been shown to have broad-ranging effects on human immunity. With regards to HIV infection, in vitro studies have shown that cocaine enhances infection of stimulated lymphocytes. Moreover, cohort studies in the pre- and post-HAART era have linked stimulant abuse with increased HIV pathogenesis. The latter data, however, have been undermined by a series of confounding factors underscoring the importance of controlled in vivo models to fully assess the impact of cocaine use and abuse on HIV infection and pathogenesis. Here, we have infected humanized mice with HIV-1 following acute cocaine exposure to assess the impact on infection. Stimulant exposure resulted in increased inflammatory cytokine expression, accelerated HIV infection, while blunting effector function of cytotoxic T lymphocytes. These data demonstrate cocaine's multifactorial impact on HIV infection that extends beyond high-risk behavior.

No MeSH data available.


Related in: MedlinePlus